Chapter 17 - Amino Acid Metabolism

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PROTEIN METABOLISM SPECIFIC WAYS OF AMINO ACIDS
CATABOLISM AND SYNTHESIS
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SPECIFIC WAYS OF AMINO ACID CATABOLISM
After removing of amino group the carbon
skeletons of amino acids are transformed into
metabolic intermediates that can be converted
into glucose, fatty acids, ketone bodies or
oxidized by the citric acid cycle.

• The carbon skeletons of 20 fundamental amino
  acids are funneled into seven molecules
• pyruvate,
• acetyl CoA,
• acetoacetyl CoA,
• ?-ketoglutarate,
• succinyl CoA,
• fumarate,
• oxaloacetate.

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Fates of carbon skeleton of amino acids
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Glucogenic vs ketogenic amino acids

• Glucogenic amino acids (are degraded to pyruvate
  or citric acid cycle intermediates) - can supply
  gluconeogenesis pathway
• Ketogenic amino acids (are degraded to acetyl CoA
  or acetoacetyl CoA) - can contribute to synthesis
  of fatty acids or ketone bodies
• Some amino acids are both glucogenic and ketogenic

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Pyruvate as an Entry Point into Metabolism
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Oxaloacetate as an Entry Point into Metabolism
Aspartate and asparagine are converted into
oxaloacetate
aspartate ?-ketoglutarate ? oxaloacetate
glutamate
Asparagine is hydrolyzed to NH4 and aspartate,
which is then transaminated.
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?-Ketoglutarate as an Entry Point into Metabolism
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Succinyl Coenzyme A Is a Point of Entry for
Several Nonpolar Amino Acids
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Methionine Degradation
S-adenosylmethionine (SAM) - a common methyl
donor in the cell
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• Homocysteine (lt 15 µmol/L)
• Hyperhomocysteinemia can results in
• Vascular diseases, endothelial dysfunction,
  atherosclerosis, thrombophilia
• Skeletal anomalies
• retardation of mental development
• Ectopic lens
• Alzheimer's disease
• Kidneys insufficiency
• Colorectal cancer

Homocysteine
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The Conversion of Branched-Chain Amino Acids
The degradative pathways of valine and isoleucine
resemble that of leucine. Isoleucine yields
acetyl CoA and propionyl CoA Valine yields CO2
and propionyl CoA.
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Degradation of Aromatic Amino Acids
Acetoacetate, fumarate, and pyruvate are common
intermediates. Molecular oxygen is used to
break an aromatic ring.
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Tryptophan degradation requires several
oxygenases
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INBORN ERRORS OF AMINO ACIDS METABOLISM
Alcaptonuria - inherited disorder of the tyrosine
metabolism caused by the absence of homogentisate
oxidase.

• homogentisic acid is accumulated and excreted in
  the urine
• turns a black color upon exposure to air

• In children
• urine in diaper may darken
• In adults
• darkening of the ear
• dark spots on the on the sclera and cornea
• arthritis

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Alcaptonuria
Arthritis of the spine is a complication of
alkaptonuria ochronosis
Accumulation of oxidized homogentisic acid
pigment in connective tissue (ochronosis)
Aortic valve stenosis in alcaptonuria
Urine turns a black color upon exposure to air
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Phenylketonuria is caused by an absence or
deficiency of phenylalanine hydroxylase or of its
tetrahydrobiopterin cofactor. Phenylalanine
accumulates in all body fluids and converts to
phenylpyruvate.

• Defect in myelination of nerves
• The brain weight is below normal.
• Mental and physical retardations.
• The life expectancy is drastically shortened.

• Diagnostic criteria
• phenylalanine level in the blood
• FeCl3 test
• DNA probes (prenatal)

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Albinism genetically determined lack or deficit
of enzyme tyrosinase Tyrosinase in melanocytes
oxidases tyrosine to DOPA and DOPA-chinone
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• Symptoms of albinism
• inhibition of production or lack of melanin in
  skin, hair, eyes
• increased sensitivity to sunlight
• increased risk of skin cancer development
• sun burns
• photophobia
• decrease of vision acuity
• strabismus, nystagmus

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Maple syrup urine disease - the disorder of the
oxidative decarboxylation of ?-ketoacids derived
from valine, isoleucine, and leucine caused by
the missing or defect of branched-chain
dehydrogenase.

• The levels of branched-chain amino acids and
  corresponding ?-ketoacids are markedly elevated
  in both blood and urine.
• The urine has the odor of maple syrup
• The early symptoms
• lethargy
• ketoacidosis
• unrecognized disease leads to seizures, coma,
  and death
• mental and physical retardation

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SYNTHESIS OF NITRIC OXIDE (NO) FROM ARGININE

• Nitric oxide (.NO) is a gas which can diffuse
  rapidly into cells, and is a messenger that
  activates guanylyl cyclase (GMP synthesis)
• NO relaxes blood vessels, lowers blood pressure,
  and is a neurotransmitter in the brain

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• Nitroglycerin is converted to NO and dilates
  coronary arteries in treating angina pectoris

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Conversion of arginine to NO via nitric oxide
synthase
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SPECIFIC WAYS OF AMINO ACID SYNTHESIS

• Plants and microorganisms can make all 20 amino
  acids
• Humans can make only 11 of the 20 amino acids
  (nonessential amino acids)
• Nonessential amino acids for mammals are usually
  derived from intermediates of glycolysis or the
  citric acid cycle
• The others are classed as "essential" amino acids
  and must be obtained in the diet

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A deficiency of even one amino acid results in a
negative nitrogen balance. In this state, more
protein is degraded than is synthesized.
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The nonessential amino acids are synthesized by
quite simple reactions. The pathways for the
formation of the essential amino acids are quite
complex.
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• The pathways for the biosynthesis of amino acids
  are diverse
• Common feature carbon skeletons come from
  intermediates of
• glycolysis,
• pentose phosphate pathway,
• citric acid cycle.

All amino acids are grouped into families
according to the intermediates that they are made
from
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